InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SMG1

Summary

InnateDB Protein

IDBP-371126.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SMG1

Protein Name

smg-1 homolog, phosphatidylinositol 3-kinase-related kinase (C. elegans)

Synonyms

61E3.4; ATX; LIP;

Species

Homo sapiens

Ensembl Protein

ENSP00000402515

InnateDB Gene

IDBG-17338 (SMG1)

Protein Structure

UniProt Annotation

Function

Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ. {ECO:0000269PubMed:11331269, ECO:0000269PubMed:11544179, ECO:0000269PubMed:15175154, ECO:0000269PubMed:16452507}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:15175154}. Cytoplasm {ECO:0000269PubMed:15175154}.

Disease Associations

Tissue Specificity

Widely expressed, with highest level in heart and skeletal muscle. Expressed in placenta, brain, lung and spleen, but not in liver. {ECO:0000269PubMed:15175154, ECO:0000269PubMed:8524286}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 43 experimentally validated interaction(s) in this database.

Experimentally validated
Total	43 [view]
Protein-Protein	43 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0044822	poly(A) RNA binding
GO:0046872	metal ion binding

Biological Process

GO:0000184	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0006281	DNA repair
GO:0006406	mRNA export from nucleus
GO:0006950	response to stress
GO:0010467	gene expression
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0016310	phosphorylation
GO:0018105	peptidyl-serine phosphorylation
GO:0046777	protein autophosphorylation
GO:0046854	phosphatidylinositol phosphorylation

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol

Protein Structure and Domains

PDB ID

InterPro

IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR003152 PIK-related kinase, FATC
IPR011009 Protein kinase-like domain
IPR014009 PIK-related kinase
IPR016024 Armadillo-type fold

PFAM

PF00454
PF02260

PRINTS

PIRSF

SMART

SM00146

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q96Q15